This project resulted in two submitted manuscripts this year and also two manuscripts that will be submitted by the end of 2008. [unreadable] [unreadable] Submitted Manuscript 1 "Low Plasma Cortisol In PTSD Is Associated With Comorbid Depression But Not With Enhanced Glucocortioid Feedback Inhibition." [unreadable] Overnight (7 p.m. to 7 a.m.) neuroendocrine measures of plasma cortisol, adrenocorticotropic hormone (ACTH), dehydroepiandrosterone sulphate (DHEA-S) were measured at 30 minute intervals in 9 subjects with PTSD without MDD, 9 with PTSD and MDD and 16 non-traumatized healthy controls. A low dose dexamethasone suppression test was administered to evaluate feedback sensitivity to glucocorticoids. Linear mixed models with body mass index (BMI) and age as covariates and Bonferroni corrected post hoc tests assessed group differences.[unreadable] [unreadable] This study found that compared to healthy controls, subjects with PTSD+MDD, but not those with PTSD-MDD, exhibited reduced plasma cortisol levels between 1:30 a.m. and 3:30 a.m. and at 4:30 a.m. and 6:30 a.m. Despite similar plasma ACTH levels between groups, ACTH/cortisol and DHEA-S/cortisol ratios were higher in PTSD+MDD patients compared to controls. We obtained identical results when the patient and control groups were re-studied one week later. Plasma DHEA-S levels and cortisol and ACTH response to a low dose dexamethasone suppression test were similar in all 3 groups. [unreadable] [unreadable] Conclusions for this study include that low plasma cortisol and high ACTH/cortisol ratio in subjects with PTSD and co-morbid MDD was not due to enhanced sensitivity to glucocorticoids feedback inhibition. Instead, this study suggests that a central abnormality is occurring and is consistent with decreased hypothalamic corticotrophin releasing hormone levels and could explain these unique findings. [unreadable] [unreadable] [unreadable] Submitted Manuscript 2 "A Multi-dimensional Investigation of Trauma Resilience"[unreadable] Compared to individuals with PTSD, resilient participants were more optimistic and had greater self-esteem and purpose in life. Resilient participants also found more meaning in the primary traumatic experience, and used greater adaptive coping strategies to deal with ongoing stressful events, such as positively reframing stressors and seeking emotional support from others. Maladaptive strategies such as self blame, behavioral disengagement and negative religious coping were less likely to be used by resilient individuals. Although resilient and PTSD participants identified the same number of supportive people in their environment, resilient participants perceived greater support from this network. Dispositional traits associated with resilience were positively correlated with an ability to find meaning in the trauma and the use of adaptive coping strategies to deal with stress. Greater purpose in life, a greater ability to develop intimate relationships and lesser use of self blame as a coping strategy, uniquely predicted resilience to trauma in a logistic regression model. Novel psychological therapies that promote resilience and prevent PTSD should be designed to enhance purpose in life, teach reappraisal of the traumatic experience, foster intimate relationships, support the use of adaptive coping styles and bolster optimism and self-esteem. [unreadable] [unreadable] Manuscript 3; In Preparation: "Emotional Intelligence in PTSD and Resilience."[unreadable] Emotional intelligence suggests that intelligence is required to process emotions, and also that emotions can increase intelligence through increasing the depth of understanding of human interactions. In this study emotional intelligence was determined by an interactive clinical interview, which is an optimal measure of this concept. Although other psychiatric disorders including depression and anxiety have been lined to insufficient emotional intelligence, PTSD has not been investigated. In this study, we found low total emotional intelligence in PTSD patients. Surprisingly, PTSD patients had high ability to perceive emotions; however their ability to manage and use emotions strategically were compromised. These findings suggest that interventions aimed at helping individuals regulate emotions may be of value to prevent and treat PTSD. [unreadable] [unreadable] Manuscript 4; "High Serial Plasma IL-6, Low Cortisol and Insufficient Regulation of IL-6 Following Hydrocortisone."[unreadable] Overnight, hourly IL-6 levels (7 p.m. to 7 a.m.) were compared, finding those patients with PTSD and depression (MDD) exhibited higher IL-6 compared to PTSD alone and also to healthy controls. In addition, all PTSD patients exhibited lower cortisol during a placebo period, and lower cortisol and greater reductions in IL-6 following hydrocortisone administration. These findings suggest that there is insufficient cortisol regulation of IL-6, in contrast to other studies that have reported increased cortisol negative feedback sensitivity. This study also provides further support of the differing biological basis of PTSD with and without depression.